Methyl iodide → 3-iodo-1-methyl-5-(trifluoromethoxy)-1H-indazole

Temperature

0 °C

To a solution of 3-iodo-5-(trifluoromethoxy)-1H-indazole (178 mg, 543 μmol) in THF (5 mL) at 0° C. was added KOtBu (85.2 mg, 760 μmol) and the mixture stirred at 0° C. for 30 min then MeI (108 mg, 47.5 μL, 760 μmol) was added. The reaction mixture was stirred at 0° C. for 30 min then warmed to 25° C. and stirred for 1.5 h. The reaction mixture was quenched with saturated ammonium chloride in water and extracted with dichloromethane (3×30 mL). The combined organics were dried over MgSO4 and concentrated to a clear oil. Purification by chromatography (40 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 20 min) gave 3-iodo-1-methyl-5-(trifluoromethoxy)-1H-indazole (141 mg, 412 μmol, 76%) as a white solid. MS (M+H)+=342.8; 1H NMR (CDCl3) δ: 7.36-7.43 (m, 1H), 7.23-7.36 (m, 2H), 4.12 (s, 3H); LCMS ESI+ TIC MS showed 100% purity, [M+H]+=342.8. The regioisomer, 3-iodo-2-methyl-5-(trifluoromethoxy)-2H-indazole, (29 mg, 84.8 μmol, 16%) was also obtained as a waxy off-white solid.

1. stirringThe reaction mixture was stirred at 0° C. for 30 min
2. temperaturethen warmed to 25° C.
3. stirringstirred for 1.5 h
4. customThe reaction mixture was quenched with saturated ammonium chloride in water
5. extractionextracted with dichloromethane (3×30 mL)
6. dry with materialThe combined organics were dried over MgSO4
7. concentrationconcentrated to a clear oil
8. customPurification by chromatography (40 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 20 min)

ORD record

ord-d3f9e6e7b44645dfb4cb57655527eb6a

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2